INTRODUCTION
Recent studies have reported the successful use of beta-
adrenergic blockers in treating infantile hemangiomas.1 In light of this new clinical application for betablockade
in pediatric dermatology, this succinct review of the
properties and current applications of available beta-adrenergic
antagonists, as well as the established treatments for infantile
hemangioma will serve as an overview for consideration of
therapeutic options in managing infantile hemangiomas.
BACKGROUND
The sympathetic autonomic response is mediated by adrenergic
receptors, the targets of intrinsic catecholamines. These receptors
are divided into alpha and beta subgroups based upon their
respective mechanisms of action and physiologic functions.
Beta-adrenergic receptors are G-protein linked and mediate the
adenylate cyclase cascade in targeted cells.2,3,4 These receptors
are further divided into 3 subclasses.
Beta-1 adrenergic receptors have an important role in cardiac
function. Stimulation yields positive inotropic and chronotropic effects,
as well as increased cardiac conduction velocity. Secondary
effects include activation of lipolysis pathways and secretion of renin
from renal juxtaglomerular cells.1 Beta-2 adrenergic receptors
primarily regulate smooth muscle and glandular function. Stimulation
results in smooth muscle relaxation, leading to vasodilation,
bronchodilation, tocolysis, down-regulation of gut motility, and
decreased bladder tone. Gluconeogenesis, glycolysis, insulin secretion,
and lipolysis are activated via the glandular effects.1 The
role of beta-3 adrenergic receptors is not fully established. These
receptors are found in gallbladder and brown adipose tissues.1
The majority of the available literature on beta receptor antagonists
and infantile hemangiomas pertains to propranolol.
Propranolol's efficacy is most probably attributable to its inhibition
of vasodilation and angiogenesis—functions associated with
beta-2 blockade.5 Individual beta-blockers have varying affinities for the receptor subclasses, leading to diverse physiologic effects.
The majority of the beta-blockers with reported use in treating
infantile hemangioma are nonspecific beta antagonists, with
activity on both beta-1 and beta-2 receptor sites. The relative cardiospecificity
of selective beta-1 antagonists renders them less
likely candidates for dermatological application, though a recently
published paper reports the successful replacement of propanolol
therapy with atenolol in 2 patients.6 In the following section, the individual
properties of available beta antagonists will be discussed.
DISCUSSION
Drugs
Alprenolol is a nonspecific beta-adrenergic inhibitor with additional
antagonist effects on serotonin 5HT-1a receptors.
Currently, alprenolol has no formal FDA approved indications
but is used off-label in adult hypertension, angina pectoris, anxiety,
hyperthyroidism, and post-myocardial infarction. Pediatric
safety and efficacy has not been established.7,8
Bucindolol is a nonspecific beta-adrenergic inhibitor with slight
alpha-adrenergic antagonistic properties. Currently, bucindolol
has no formal FDA approved indications but has been used
off-label in adult congestive heart failure and hypertension. Pediatric
safety and efficacy has not been established.9,10
Carteolol is a nonspecific beta-adrenergic inhibitor. FDA approved
indications for its use include adult hypertension, adult
ocular hypertension, and adult open-angle glaucoma. Carteolol
is used off-label in angina, arrhythmia, congestive heart failure,
post-myocardial infarction, anxiety, panic attacks, aggressive behavior,
and neuroleptic-induced akathisia. Pediatric safety and
efficacy has not been established. Carteolol is available as an
ophthalamic solution or an oral tablet.11
